Researchers will develop tools that simplify analysis of glycans, biomolecules more diverse than the genome

“They are by orders of magnitude more diverse than the genome, and represent the next challenging frontier in the biological sciences.”

Stefan Ruhl, principal investigator and professor in the Department of Oral Biology in the UB School of Dental Medicine

BUFFALO, N.Y. – A University at Buffalo-led team of
researchers has received a $1.35 million grant from the National
Institutes of Health (NIH) Common Fund for Glycoscience to increase
knowledge of glycans, a common but little understood class of
biomolecules that help bacteria attach to host surfaces, including
those in the mouth.

The three-year grant will allow the researchers to collect oral
bacteria from humans, horses, cows, sheep, rodents and other
mammals. The goal is to harness tools that ultimately help
scientists examine how the microorganisms bind to glycans in the
mouth to form dental biofilms – more commonly known as plaque
– increasing the risk for cavities and periodontal
disease.

Glycans exist throughout the body within all living organisms
and vary between species and by the individual. Yet, due to their
incredibly complex structure, little is known about their
biological functions and roles in disease.

Bacteria attach to host tissues by building custom appendages
called adhesins that enable them to bind to their host’s
glycans. However, to prevent being targeted by pathogens, new
glycan structures are invented by the host.

The constant changes force bacteria to play catch up by evolving
with the host. Researchers, on the other hand, have difficulties
keeping up with the study of glycans due to the need for complex
analyses that can only be completed in specialized labs outfitted
with expensive equipment.

“We know too little about their function in health and
disease. They are by orders of magnitude more diverse than the
genome, and represent the next challenging frontier in the
biological sciences.”

The research is one of several projects supported through the
NIH Common Fund for Glycoscience, and is the only one that includes
dental research. The study is also led by Paul Sullam, MD,
co-principal investigator and professor in the Department of
Medicine at the University of California, San Francisco.

The project includes additional investigators from UB;
University of California, San Francisco; University of California,
San Diego; University of California, Davis; University of Maryland;
Emory University and Cornell University.

The study will use friendly bacteria harvested from the mouths
of humans and animals to mine for serine-rich repeat (SRR)
proteins, a well-studied class of bacterial adhesins that are
highly variable and able to bind to a wide range of glycans.

Using genetic information, the researchers will artificially
reproduce the variable, glycan binding pockets of SRR proteins.
After testing the proteins for their ability to bind to their
target glycans, the adhesins will be mass produced to create
affordable, easy-to-use toolkits for scientists who are interested
in glycan analysis, but lack expertise in glycoscience.

“We do not need to invent such tools. Nature has already
created them for us. They are ready and out there. All we do here
is to harvest them straight from the mouth,” says Ruhl.

Since bacteria evolved to match the glycans in their host
environment, the adhesins will offer clues to patterns and
characteristics within the millions of potential glycan structures
in both biological and pathological samples.

To learn more about the research being completed under the NIH
Common Fund for Glycoscience, visit http://bit.ly/2z7Izbf.